Journal of Clinical Endocrinology & Metabolism, Vol 65, 59-64, Copyright © 1987 by Endocrine Society

ARTICLES

Relationship of islet function to insulin action in human obesity

JC Beard, WK Ward, JB Halter, BJ Wallum and D Porte Jr

To analyze B-cell mechanisms in obesity, we measured the relationship (slope of potentiation) between glucose levels and acute insulin responses (AIR) to isoproterenol or arginine in nondiabetic subjects ranging from lean to markedly obese. Obese men (n = 9) had higher AIRs to isoproterenol than lean men (n = 11) at basal glucose levels [52 +/- 9 (SEM) vs. 32 +/- 5 microU/mL; P less than 0.05], and the difference increased as the ambient glucose level was raised (at 230 mg/dL; 263 +/- 22 vs. 140 +/- 21 microU/mL; P less than 0.0008). The individuals' slopes of glucose potentiation of AIR to isoproterenol were positively correlated with their excess weight (r = 0.72; P less than 0.001). Similar results were found when arginine was used as the secretagogue in other men and in women; the slope of potentiation was positively correlated with excess weight in both men and women (both P less than 0.005), although the effect of excess weight on slope was 51% greater among men (P less than 0.03). An independent measurement of insulin sensitivity (the Bergman SI) was made in the women. The potentiation slope was inversely correlated with SI (P less than 0.0001), indicating that the effect of obesity on insulin secretion is correlated with insulin resistance. These results characterize one mechanism contributing to the hyperinsulinemia of obesity and highlight the importance of considering the prevailing insulin sensitivity when assessing islet function.

This article has been cited by other articles:

				M. Sjostrand, S. Gudbjornsdottir, L. Strindberg, and P. Lonnroth Delayed Transcapillary Delivery of Insulin to Muscle Interstitial Fluid After Oral Glucose Load in Obese Subjects Diabetes, January 1, 2005; 54(1): 152 - 157. [Abstract] [Full Text] [PDF]

				R. J. Norman, M. Noakes, R. Wu, M. J. Davies, L. Moran, and J. X. Wang Improving reproductive performance in overweight/obese women with effective weight management Hum. Reprod. Update, May 1, 2004; 10(3): 267 - 280. [Abstract] [Full Text] [PDF]

				M. J. Holness, N. D. Smith, G. K. Greenwood, and M. C. Sugden Acute {omega}-3 Fatty Acid Enrichment Selectively Reverses High-Saturated Fat Feeding-Induced Insulin Hypersecretion But Does Not Improve Peripheral Insulin Resistance Diabetes, February 1, 2004; 53(90001): S166 - 171. [Abstract] [Full Text]

				M. C. Sugden, G. K. Greenwood, N. D. Smith, and M. J. Holness Peroxisome Proliferator-Activated Receptor-{alpha} Activation during Pregnancy Attenuates Glucose-Stimulated Insulin Hypersecretion in Vivo by Increasing Insulin Sensitivity, without Impairing Pregnancy-Induced Increases in {beta}-Cell Glucose Sensing and Responsiveness Endocrinology, January 1, 2003; 144(1): 146 - 153. [Abstract] [Full Text] [PDF]

				M. Sjostrand, S. Gudbjornsdottir, A. Holmang, L. Lonn, L. Strindberg, and P. Lonnroth Delayed Transcapillary Transport of Insulin to Muscle Interstitial Fluid in Obese Subjects Diabetes, September 1, 2002; 51(9): 2742 - 2748. [Abstract] [Full Text] [PDF]

				S. M. Chalkley, M. Hettiarachchi, D. J. Chisholm, and E. W. Kraegen Long-term high-fat feeding leads to severe insulin resistance but not diabetes in Wistar rats Am J Physiol Endocrinol Metab, June 1, 2002; 282(6): E1231 - E1238. [Abstract] [Full Text] [PDF]

				S. E. Kahn The Importance of {beta}-Cell Failure in the Development and Progression of Type 2 Diabetes J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4047 - 4058. [Full Text] [PDF]

				S. E. Kahn, R. L. Prigeon, R. S. Schwartz, W. Y. Fujimoto, R. H. Knopp, J. D. Brunzell, and D. Porte Jr. Obesity, Body Fat Distribution, Insulin Sensitivity and Islet {{beta}}-Cell Function as Explanations for Metabolic Diversity J. Nutr., February 1, 2001; 131(2): 354S - 360. [Abstract] [Full Text]